International HapMap Consortium Expands Mapping Effort Map of Human Genetic Variation Will Speed Search for Disease Genes
Bethesda, Maryland – The International
HapMap Consortium, boosted by an additional $3.3 million in public-private
support, today announced plans to create an even more powerful
map of human genetic variation than originally envisioned. The
map will accelerate the discovery of genes related to common diseases,
such as asthma, cancer, diabetes and heart disease.
When the project was launched in October 2002, the consortium
set September 2005 as the target for completing its map of common
patterns of human genetic variation, also known as haplotypes.
By the end of February 2005, however, the group already will have
reached completion of its first draft of the human haplotype map,
or HapMap, which will consist of 1 million markers of genetic variation,
called single nucleotide polymorphisms (SNPs).
The consortium’s new goal is to build an improved version
of the HapMap that is about five times denser than the original
plan. This “Phase II” HapMap will take advantage of
the rapid, high-throughput genotyping capacity of Perlegen Sciences,
Inc., of Mountain View, Calif., to test another 4.6 million SNPs
from publicly available databases, and add that information to
the map. As a result of a grant competition last summer, Perlegen
received a $6.1 million award from the National Human Genome Research
Institute (NHGRI), part of the National Institutes of Health (NIH),
to add data on 2.25 million additional SNPs to HapMap. The new
development, enabled by a partnership among multiple funding sources,
will expand that effort and test virtually the entire known catalog
of human variation on the HapMap samples. This will increase the
density of SNP “signposts” across the genome from the
current average of one every 3,000 bases to about one every 600
bases.
“This will help us create a far more powerful HapMap than
we ever imagined. We sincerely thank all those who are giving their
time, technology and money to help turn this dream into reality.
The payoff will be a better understanding of the genetic risk factors
underlying a wide range of diseases and conditions,” said
NHGRI Director Francis S. Collins, M.D., Ph.D.
The first phase of the HapMap Project has allowed scientists to
make important analyses of the human genome that were not possible
with just the human DNA sequence, and the International HapMap
Consortium plans to publish its comprehensive analysis of this
data later this year. The second phase of the project will provide
researchers with a denser map that will enable them to more precisely
narrow gene discovery to specific regions of the genome.
The effort to expand the HapMap is made possible by $3.3 million
in additional support from a unique public-private partnership,
including the following organizations: the Wellcome Trust, London,
$624,000; Genome Canada/Genome Quebec, $260,000; Bristol-Myers
Squibb Co., New York, $100,000; Pfizer Inc., New York, $100,000;
Perlegen Sciences, at least $1.2 million (based on “in kind” services);
and NHGRI, $1 million. The donations from the two pharmaceutical
companies were coordinated by The SNP Consortium, Ltd., of Deerfield,
Ill.
“Researchers are already using HapMap data to accelerate
the search for genes involved in common diseases, as well as genes
involved in drug responsiveness,” said Karen Kennedy, Ph.D.,
science program manager at the Wellcome Trust. “When the
more comprehensive version of the HapMap is completed this fall,
such studies will be able to be carried out with even greater speed
and efficiency.”
To create the HapMap, DNA was taken from blood samples from volunteer
donors from the following populations: Han Chinese in Beijing,
Japanese in Tokyo, Yoruba in Ibadan, Nigeria and Utah residents
with ancestry from northern and western Europe. No medical or personal
identifying information was obtained from the 270 donors. However,
the samples are identified by the population from which they were
collected.
Although any two people are 99.9 percent identical at the genetic
level, understanding the one-tenth of one percent difference is
important because it helps explain why one person may be more susceptible
to a certain disease than another. For any given disease, such
as type II diabetes or coronary artery disease, researchers can
use the HapMap to compare the genetic variation patterns of a group
of people known to have the disease with a group of people without
the disease. Finding a certain pattern more often in people with
the disease identifies a genomic region that may contain genes
contributing to the condition. Because the Phase II HapMap will
be so detailed, researchers will be able to use its SNP signposts
to zero in on that particular genomic region and search for specific
genes involved in that disorder. This approach can reduce the work
and expense of searching the genome for hereditary factors in common
disease by a factor of 20 to 40 compared with current, brute force
approaches.
“This new partnership underscores the private sector’s
enthusiasm for the HapMap and its potential as a tool for the understanding
of disease. The willingness of these firms to contribute to building
an even better map follows the collaborative tradition established
by The SNP Consortium,” said Arthur Holden, chairman and
chief executive of The SNP Consortium.
In addition to affecting risk of disease, genetic variation has
been shown to affect the response of people to therapeutic drugs,
toxic substances and environmental factors, and the HapMap can
assist in the identification of those variants. Since not all genetic
variants are deleterious, the HapMap also may be used to help to
pinpoint genetic variations that contribute to good health, such
as those protecting against infectious diseases or promoting longevity.
“We are excited by the opportunity to apply our technology
to all publicly available SNPs. This effort is so important that
Perlegen is willing to contribute some of its own resources to
make this possible,” said Kelly A. Frazer, Ph.D., vice president
of genomics at Perlegen. “We are confident that the end result
of this public-private collaboration will be an outstanding human
haplotype map that will provide a major new tool in the effort
to combat human disease through an understanding of its genetic
components.”
Researchers around the globe can quickly access the HapMap data
through free public databases, such as the HapMap Data Coordination
Center (http://www.hapmap.org), the NIH-funded National Center
for Biotechnology Information’s dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/)
and the JSNP Database in Japan (http://snp.ims.u-tokyo.ac.jp/).
“Adding this large number of new SNPs to the map will make
it even easier for researchers to correlate genetic variation with
gene function. Such information is crucial for the development
of therapies and preventive strategies tailored to each person’s
unique genetic makeup,” said Martin Godbout, Ph.D., president
and CEO of Genome Canada, who also was speaking on behalf of Genome
Quebec.
The International HapMap Consortium is a public-private partnership
of scientists and funding agencies from Canada, China, Japan, Nigeria,
the United Kingdom and the United States. The U.S. component of
the $135 million international project is led by NHGRI on behalf
of the 19 institutes, centers and offices of the NIH that contributed
funding. For more information on the International HapMap Project,
see http://genome.gov/10001688 or http://www.hapmap.org/. To see
a complete list of participating research organizations, see http://www.hapmap.org/groups.html.
NHGRI is one of the 27 institutes and centers at the NIH, which
is an agency of the Department of Health and Human Services. The
NHGRI Division of Extramural Research supports grants for research
and for training and career development at sites nationwide. Additional
information about NHGRI can be found at www.genome.gov.
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